Comparative evolution of influenza A virus H1 and H3 head and stalk domains across host species

Nidia S. Trovão, Sairah M. Khan, Philippe Lemey, Martha I. Nelson, Joshua L. Cherry

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The influenza A virus hemagglutinin protein (HA) has been studied extensively in humans but less so in other host species. Here, we compared the rates of nucleotide substitution, protein evolution, and glycosylation in the H1 and H3 head and stalk domains among five host classes (avian, canine, equine, human, and swine). For further resolution, we separately analyzed 49 lineages differentiated by host and geography. HA evolution in non-human hosts was more dynamic than expected. For example, the classical swine H1 head domain accumulated glycosylation sites in the antigenically important head domain at a rate as high as in humans. However, whereas the stalk domain was highly conserved in humans, with a low ratio of non-synonymous to synonymous changes, this ratio was approximately 2.5-fold higher in canines. Together, these findings highlight the need for further study of HA evolution in non-human hosts.

Original languageEnglish
Issue number1
StatePublished - Jan 2024
Externally publishedYes


  • adaptive evolution
  • glycosylation
  • hemagglutinin
  • influenza A virus
  • inter-species transmission
  • phylodynamics


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